Genomic Analyses of Intraspecific Patterns of Extreme Recombination in Honey Bees

描述（由申请人提供）：我的长期目标是在基因组水平上了解社会进化的原因和后果，使用蜜蜂作为科学模型。迄今为止在蜜蜂中发现的最重要的基因组特征是它们异常高的基因组重组率。蜜蜂基因组重组率的强烈上调尚未被详细研究，尽管对其模式和机制的研究可能会为我们理解DNA重组产生相关的见解，并对DNA修复，基因组稳定性，癌症生物学，病原体的遗传变异以及人类健康产生影响。 基于以前的发现，蜜蜂表现出最高的基因组重组率的所有后生动物和大量的后代数量的个人蜂后，我建议研究的模式，在蜜蜂基因组中的重组详细。该项目将测试的预测，非常高的重组率在蜜蜂是与重组的高度可变性，由于最近提出的进化动力学的减数分裂重组的调节。 预测将通过解决以下三个具体目标进行测试：1。构建了我国第一张高密度连锁图谱。本研究利用具有成本效益的RAD标签标记来研究重组的精细尺度模式并表征重组热点。2. A.重组率的种内变异特征。通过对来自不同群体的90只不同蜂王的后代进行基因分型，选择连锁标记，在特定的基因组区域对意大利蜜蜂进行基因分型。3.通过比较年轻和年老蚁后后代以及氧化应激暴露前后蚁后的连锁标记之间的重组率，研究选定基因组区域重组率的个体内变异。 受最近的方法学进展和对基因组重组调控的兴趣的启发，这一建议是及时和创新的。它涉及与人类健康有多种联系的基本生物过程。它将提供新的见解，阐明特定的研究系统，同时也有助于我们对减数分裂重组及其变异性的总体了解。它将产生数据，以产生新的假设，作为未来研究的基础。此外，对这项研究的资助将加强UNCG生命科学的研究环境，特别是我们部门新设立的博士课程。最后，它将使我能够扩大我的奉献精神，指导学生的研究和培养下一代的生命科学家。 公共卫生相关性：除了作为授粉者的重要性外，蜜蜂还可以告诉我们DNA重组，这是一个与多种遗传疾病和癌症有关的过程。这项研究计划将研究蜜蜂的过度重组率，以了解它与人类重组的可比性。它还将研究重组如何受到衰老和压力的影响，以得出可能适用于理解人类基因组完整性的一般结论。此外，我将培训和指导生物医学研究的学生，以促进下一代生命科学家。

DESCRIPTION (provided by applicant): My long-term goal is to understand causes and consequences of social evolution at the genome level, using honeybees as scientific model. The most important genomic feature discovered in honeybees so far is their exceptionally high genomic recombination rate. The strong up regulation of the genomic recombination rate in honeybees has not been studied in detail, although the investigation of its patterns and mechanisms may yield relevant insights for our understanding of DNA recombination with implications for DNA repair, genomic stability, cancer biology, genetic variation of pathogens, and thus human health. Based on the previous finding that honeybees exhibit the highest genomic recombination rate of all metazoans and the large offspring number of individual honeybee queens, I propose to study the patterns of recombination in the honeybee genome in detail. The project will test the prediction that the extraordinarily high recombination rate in honeybees is associated with a high variability in recombination due to the recently proposed evolutionary dynamics of the regulation of meiotic recombination. The prediction will be tested by addressing the following three specific aims: 1. Construction of the first high-density linkage map for A. mellifera with cost-effective RAD-tag markers to study the fine-scale patterns of recombination and characterize recombinational hotspots. 2. Characterization of intra-specific variation in recombination rate in A. mellifera in specific genome regions by genotyping selected linked markers in offspring of 90 different queens from different populations. 3. Study of the intra-individual variation of recombination rates in selected genome regions by comparing recombination rates between linked markers in offspring of young and old queens and from queens before and after oxidative stress exposure. Motivated by recent methodological advances and interest in the regulation of genomic recombination, this proposal is timely and innovative. It addresses a fundamental biological process with multiple connections to human health. It will provide novel insights that illuminate the particular study system but also contribte to our general understanding of meiotic recombination and its variability. It will produce data to generate new hypotheses as basis for future research. Furthermore, funding for this research will strengthen the research environment in the life sciences at UNCG, particularly with respect to the newly established PhD program in our department. Finally, it would allow me to expand my dedication to mentoring student research and fostering the next generation of life scientists. PUBLIC HEALTH RELEVANCE: In addition to its importance as pollinator, the honeybee can also inform us about DNA recombination, a process that is related to multiple genetic disorders and cancer. This research program will study the excessive recombination rate of honeybees to learn how comparable it is to human recombination. It will also study how recombination is affected by aging and stress to draw general conclusion that may be applicable to understand genome integrity in humans. Furthermore, I will train and mentor students in biomedical research to promote the next generation of life scientists.